Identification of an alternatively spliced nuclear isoform of human N-terminal acetyltransferase Naa30

N-terminal acetylation is a highly abundant and important protein modification in eukaryotes catalyzed by N-terminal acetyltransferases (NATs). In humans, six different NATs have been identified (NatA-NatF), each composed of individual subunits and acetylating a distinct set of substrates. Along with most NATs, NatC acts co-translationally at the ribosome. The NatC complex consists of the catalytic subunit Naa30 and the auxiliary subunits Naa35 and Naa38, and can potentially Nt-acetylate cytoplasmic proteins when the initiator methionine is followed by a bulky hydrophobic/amphipathic residue at position 2. Here, we have identified a splice variant of human NAA30, which encodes a truncated protein named Naa30₂₈₈. The splice variant was abundantly present in thyroid cancer tissues and in several different human cancer cell lines. Surprisingly, Naa30₂₈₈ localized predominantly to the nucleus, as opposed to annotated Naa30 which has a cytoplasmic localization. Full-length Naa30 acetylated a classical NatC substrate peptide in vitro, whereas no significant NAT activity was detected for Naa30_288. Due to the nuclear localization, we also examined acetyltransferase activity towards lysine residues. Neither full-length Naa30 nor Naa30₂₈₈ displayed any lysine acetyltransferase activity. Overexpression of full-length Naa30 increased cell viability via inhibition of apoptosis. In contrast, Naa30₂₈₈ did not exert an anti-apoptotic effect. In sum, we identified a novel and widely expressed Naa30 isoform with a potential non-catalytic role in the nucleus.